Skyscrapers, which reflects the 1920s precisionist aesthetic, is one of Sheeler's most accomplished assimilations of European modernism into his own uniquely American style. Using sharply defined contours, non-atmospheric planes of color, and intense frontal light, Sheeler conveyed the grandeur of monumental buildings grouped together.

Sheeler's interest in skyscraper imagery was heightened by his collaboration with photographer Paul Strand on the 1920 film Manhatta. Sheeler found one view included in the film particularly interesting—the back of the Park Row building seen from the 41-story Equitable Building at 120 Broadway, a site he captured in a series of photographs. Before painting an image, Sheeler often took preparatory photographs and made pencil drawings of a desired scene. This process lent itself to highly detailed and precise renderings in his paintings.

For Skyscrapers, Sheeler made and studied both a photograph and a drawing. In comparing the photograph and the drawing with the final work, one can visualize Sheeler’s gradual reduction and simplification of the scene. By cropping the image, he brought the subject closer to the picture plane. In the painting, Sheeler simplified the image by creating planes of solid color for the shapes that are crucial to the overall structure of the composition. The viewer's eye is directed into the composition by the diagonal recession of strong gray shadows. Intended as a unifying compositional device rather than a disclosure of time of day, these raking shadows converge on the focal point of the painting, the cubic design in the lower center of the picture. The diagonal contours of the shadows disrupt the otherwise predominantly vertical composition.

Recognizing Sheeler's contribution to the expansion of American modernism, Phillips included Skyscrapers in his 1926 exhibition of young American modernist painters. Anticipating a negative and confused reaction from the public, Phillips wrote: "Art must either be content to remain in the museum, withdrawn from the highways of our active life, or it must be insinuated somehow into the new scheme of things. The artists … must therefore find elements of beauty in the new world…." In Skyscrapers, Sheeler elicited beauty from the stark reality of New York office buildings and the utilitarian aspects of industrial America.